Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm

International audiencePURPOSE Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a unique myeloid malignancy with CD123 interleukin-3 receptor-α overexpression and poor prognosis. METHODS This phase I/II, open-label, multicenter study evaluated pivekimab sunirine (PVEK), a novel CD123 antibody-drug conjugate, 0.045 mg/kg once every 3 weeks, in adults with frontline (no previous systemic therapy and de novo BPDCN or coexisting hematologic malignancy) or relapsed/refractory BPDCN (ClinicalTrials.gov identifier: NCT03386513 ) The primary end point in the primary analysis population (PAP; frontline de novo) was composite complete response (CCR; CR+ clinical CR) rate. RESULTS Of 84 patients, 33 had frontline BPDCN (22 de novo [20 in PAP]; 11 with previous or concomitant malignancy) and 51 had relapsed/refractory disease. The median (range) age was 72 (63-76) years. In the PAP (n = 20), the CCR rate was 75% (95% CI, 51 to 91; n = 15; median duration: 10.6 [95% CI, 3.8 to not reached] months) and the median overall survival (OS) was 16.6 (95% CI, 7.2 to not reached) months. Eight of these 15 (53%) patients proceeded to stem-cell transplant (SCT). The corresponding rate for relapsed/refractory disease was 14% (95% CI, 6 to 26; n = 7; median duration: 9.2 [95% CI, 2.4 to not reached] months), and the median OS was 5.8 (95% CI, 3.9 to 8.4) months. Adverse events (AEs) included peripheral edema (54%), fatigue (26%), and infusion-related reactions (26%). Grade ≥3 events included neutropenia (16%), thrombocytopenia (14%), and peripheral edema (12%). Serious AEs included pneumonia (6%) and febrile neutropenia (5%). Two on-treatment cases of reversible veno-occlusive disease (VOD) occurred. Of the total 19 patients who proceeded to SCT, VOD was reported in five patients (four with relapsed/refractory BPDCN). CONCLUSION PVEK, with convenient dosing, led to high, durable responses, especially in frontline BPDCN, and a manageable safety profile

P0805 Predictors of Endoscopic Remission at 1 Year in Patients with Ulcerative Colitis Treated with Guselkumab: Post-hoc Analyses of the QUASAR Trial

International audienceBackground Ulcerative colitis (UC) management aims to achieve sustained clinical remission and long-term endoscopic and histological healing. In the Phase 2b/3 QUASAR trial in UC, guselkumab (GUS) significantly improved clinical remission by Week (W) 44 of the maintenance (M) study, with one-third of patients (pts) achieving endoscopic remission (ER; endoscopic Mayo subscore [EMS]=0).1 Post-hoc analyses of QUASAR evaluated predictors of ER at 1 year of GUS treatment in pts with moderately-to-severely active UC. Methods In the maintenance study of QUASAR, GUS (intravenous 200mg at W0, W4, and W8) responders at W12 of the induction study were re-randomized to receive subcutaneous (SC) GUS 100mg every 8W (Q8W), GUS 200mg SC Q4W, or placebo. Data from pts re-randomized to GUS were analyzed. Predictors of ER at M-W44 were assessed via logistic regression. Univariate models were run for each variable of interest at induction and M-baseline (BL). Variables with p < 0.1 were entered into reduced multivariate models using stepwise backward selection (Wald method); separate models were run for induction BL and M-BL variables. Results Of 378 GUS responders re-randomized to GUS 100mg SC Q8W or GUS 200mg SC Q4W, 129 (34%) achieved M-W44 ER. Rates of M-W44 ER did not differ across GUS regimens. In univariate models, induction BL factors associated with achieving M-W44 ER included female sex, extensive UC, concomitant oral aminosalicylate use, elevated C-reactive protein levels (CRP; >3mg/L), and no prior advanced drug therapy (ADT) failure (Table 1; Table 2). At M-BL, lower CRP (≤3mg/L or ≥ 50% reduction from induction BL) and fecal calprotectin (FC; ≤250μg/g or ≥ 50% reduction from induction BL) levels, and endoscopic healing (EMS=0 or 1) were also individually associated with M-W44 ER. After adjusting for GUS regimen, female sex (odds ratio [OR] [95% confidence interval; CI]: 1.8 [1.2, 2.9]; nominal P = 0.007), extensive UC (1.8 [1.2, 2.9]; nominal P = 0.007), and concomitant oral aminosalicylate use (1.9 [1.1, 3.4]; nominal P = 0.022) were identified as independent induction BL predictors of M-W44 ER. Achievement of endoscopic healing (3.1 [1.9, 4.9]; nominal P < 0.0001) at M-BL was independently associated with M-W44 ER. Conclusion Among GUS responders in the QUASAR maintenance study, female sex, extensive UC, and concomitant oral aminosalicylate use at induction BL were independently associated with ER at 1 year of GUS treatment. Importantly, achieving endoscopic healing after induction (i.e., at M-BL) was strongly associated with higher likelihood of ER at 1 year, irrespective of GUS dosing regimen, suggesting that this factor may help inform long-term endoscopic outcomes. Reference: 1. Rubin DT, Allegretti JR, Panés J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49. doi:10.1016/S0140-6736(24)01927-5. Conflict of interest: Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Baker, Thomas: Employee of Johnson & Johnson Alvarez, Yelina: Employee of Johnson & Johnson Bravatà, Ivana: Employee of Johnson & Johnson Nazar, Maciek: Employee of Johnson & Johnson Van Denderen, Jacqueline: Employee of Johnson & Johnson Mccaffrey, Victoria: Employee of Johnson & Johnson Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris

La place de l’Histoire du droit et des institutions dans les pensées libertaires

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Cohomological integrality for symmetric quotient stacks

In this paper, we establish the sheafified version of the cohomological integrality conjecture for stacks obtained as a quotient of a smooth affine symmetric algebraic variety by a reductive algebraic group equipped with an invariant function. A crucial step is the definition of the BPS sheaf as a complex of monodromic mixed Hodge modules. We prove the purity of the BPS sheaf when the situation arises from a smooth affine weakly symplectic algebraic variety with a weak moment map. This situation gives local models for 1-Artin derived stacks with self-dual cotangent complex. We then apply these results to prove a conjecture of Halpern-Leistner predicting the purity of the Borel-Moore homology of $0$-shifted symplectic stacks (or more generally, derived stacks with self-dual cotangent complex) having a proper good moduli space. One striking application is the purity of the Borel--Moore homology of the moduli stack of principal Higgs bundles over a smooth projective curve for a reductive group

Clinical characteristics and treatments of imported loiasis patients with microfilaraemia diagnosed in France, 2000-2022

International audiencentroductionLoiasis has been associated with increased morbidity and mortality, particularly in cases of high microfilarial density. Treatment depends on initial microfilaraemia (Mf) and relies on ivermectin (IVM), diethylcarbamazine (DEC) or albendazole (ALB), all associated with serious adverse events. Our objective was to describe the clinical characteristics, management and outcomes of patients diagnosed with loiasis and Mf in France.MethodsWe conducted a multicenter retrospective study including patients with loiasis and Mf diagnosed and treated in France between 2000-2022, with at least one follow-up evaluation. We collected clinical and biological data, including Mf kinetics, for each treatment episode.ResultsA total of 150 patients (181 treatment episodes) were included across 27 centers. Median age was 35 years, and most patients presented symptoms (75.3%). Median Mf was 500 mf/ml; for 74% of episodes, baseline Mf below 2000 mf/ml, while 8% had baseline Mf above 8000 mf/ml. Twelve different treatment schemes were identified, the most common being a single dose of IVM (39%). Adverse events occurred in 12% of episodes, including one fatal event. On last follow-up visit, 9.3% of patients still experienced symptoms, 24.7% exhibited persistent Mf, and 19.3% had persistent blood eosinophilia, patients treated with stand-alone IVM experienced worse outcomes (18%, 72% and 39%, respectively).ConclusionIn France, loiasis treatment is inconsistent and frequently relies on inadequate options, including IVM monotherapy, which lacks therapeutic efficacy, and carries safety concerns. Our findings highlight real-world practices and indicates that better training is needed for practitioners treating patients with loiasis

A PDE model of forest plants interactions: Mathematical analysis and PINN-based simulations

International audienceForest ecosystems are shaped by complex, multispecies interactions that unfold over space and time. Traditional models of forest dynamics often neglect these interactions, particularly the spatial and competitive processes critical for understanding community-level outcomes. To address these limitations, we present a novel spatially explicit model that integrates light-mediated competition among multiple tree species using a system of nonlinear reaction-diffusion partial differential equations. Our approach incorporates the Beer-Lambert law to model asymmetric competition for light within a forest canopy, enabling more realistic simulation of species growth, dispersal, and coexistence. To enhance model calibration and data integration, we employ Physics-Informed Neural Networks, an emerging technique that merges observational data with mechanistic theory. We apply this framework to three species in the Compiègne Forest, namely Fagus sylvatica (European beech), Pinus sylvestris (Scots pine), and one invasive Prunus serotina (black cherry), to explore their spatial dynamics and competitive outcomes. This study demonstrates the power of hybrid mechanistic and data-driven approaches for advancing forest dynamics modeling

Splitting methods for the Gross-Pitaevskii equation on the full space and vortex nucleation

We prove the convergence in Zhidkov spaces of the first-order Lie-Trotter and the second-order Strang splitting schemes for the time integration of the Gross-Pitaesvkii equation with a time-dependent potential and non-zero boundary conditions at infinity. We also show the conservation of the generalized mass and the near-preservation of the Ginzburg-Landau energy balance law. Numerical accuracy tests performed on a one-dimensional dark soliton corroborate our theoretical findings. We finally investigate the nucleation of quantum vortices in two experimentally relevant settings

Characterisation of the Novel HLA‐C*03:741 Allele by Next Generation Sequencing

International audienceHLA‐C*03:741 differs from the HLA‐C*03:04:01:01 allele by one non‐synonymous nucleotide at position 729 in exon 2

Effects of Microplastics and Nanoplastics on the Kidneys

International audiencePlastics are hydrophobic carbon polymers with a half-life of approximately 500 years. The widespread production and environmental accumulation of plastics pose significant toxicity concerns. Humans are routinely exposed to micro- and nanoplastics (MNPs), which can enter rate the bloodstream and reach various organs, including the kidneys. Here, we review research on nephrotoxic effects of plastics and the underlying mechanisms. The results of several studies of kidneys in mammals and kidney cells from humans suggest that MNPs induce renal toxicity. Although the underlying mechanisms remain to be characterized in detail, the current body of evidence suggests that MNPs promote the production of reactive oxygen species and thus trigger local (renal) and systemic inflammatory responses. These processes enhance cytotoxicity and may drive MNP-induced kidney damage. This toxicity results in histopathological changes in renal tissues (including glomerular and tubular damage and fibrosis) and modifications in key biomarkers of renal function (such as the glomerular filtration rate, albuminuria, and the blood urea nitrogen level). Moreover, MNPs have been shown to induce cardiovascular damage, which may contribute to the progression of chronic kidney disease (CKD) - potentially via the activation of aryl hydrocarbon receptors. Notably, the nephrotoxic effects of MNPs appear to be exacerbated by co-exposure to other environmental contaminants and uremic toxins. CKD can impair the kidneys' ability to eliminate MNP. Furthermore, dialyzed patients are substantially exposed to MNPs during dialysis sessions, which potentially compounds their vulnerability. With a view to better understanding the effects of MNPs on renal health and the impact of CKD and dialysis on levels of exposure to plastics, further studies are essential

Deep Learning for Automated Classification of Liver Tumours on Digitalized Liver Biopsies: An Unsupervised and Semi- Supervised Approach

International audienceBackground&Aims: Automated classification of hepatic tu- mours on liver biopsies remains challenging due to morpholog- ical overlaps. We developed deep learning models to discrimi- nate hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and metastatic lesions on digitalized whole slide images (WSI).Methods: We retrospectively analysed 210 liver biopsy samples from 204 patients (2020-2025) at the University of Palermo, in- cluding HCC (n=84), intrahepatic CCA (n=34), hepatocholangiocar- cinoma (n=4), liver metastases (n=65), and non-neoplastic sam- ples (n=23). WSI were digitized in NDPI format. Initially, we ap- plied unsupervised learning: WSI were segmented into 512 × 512px patches, deep features extracted using pre-trained ResNet-50, di- mensionality reduction performed with UMAP, and clustering ex- ecuted with HDBSCAN followed by agglomerative merging. Subse- quently, we developed a semi-supervised Mean Teacher model us- ing 30% expert-annotated WSI and 70% unlabeled data with con- sistency regularization.Results: Unsupervised clustering achieved low purity: Cluster 0 (42% HCC, 11% CCA, 47% negative), Cluster 1 (35% HCC, 16% CCA, 48% negative), demonstrating inadequate class discrimination. The semi-supervised model achieved markedly superior performance: 97.85% training accuracy and 89.24% validation accuracy. Starting from limited annotations (30%), the model effectively generated high-quality pseudo-labels for the unlabeled majority, learning ro- bust features despite class imbalance and successfully discriminat- ing between hepatic tumour types.Conclusions: Semi-supervised learning significantly outper- formed unsupervised approaches for hepatic tumour classification. This model shows promise as a first-line screening tool in liver biopsies to optimize diagnostic workflow and guide immunohisto- chemical panel selection, serving as an assistant for junior pathol- ogists and quality assurance instrument in low-volume centres